Vol.:(0123456789) 1 3
Medical Oncology (2018) 35:157
https://doi.org/10.1007/s12032-018-1222-4
ORIGINAL PAPER
Autotaxin is a novel molecular identifer of type I endometrial cancer
Antonio Mazzocca
1
· Luca Maria Schönauer
2
· Rosalba De Nola
2,3
· Antonio Lippolis
2
· Teresa Marrano
2
·
Matteo Loverro
2
· Carlo Sabbà
1
· Edoardo Di Naro
2
Received: 10 September 2018 / Accepted: 25 October 2018 / Published online: 29 October 2018
© Springer Science+Business Media, LLC, part of Springer Nature 2018
Abstract
Endometrial cancer is the most common cancer of the female genital tract in Western Countries, with an incidence of 150.000
new cases/year. Despite high incidence, little is known about the molecular pathogenesis of this tumor. Phospholipids
including lysophosphatidic acid (LPA) are involved in proliferation and dissemination of cancer. LPA is a potent bioactive
phospholipid synthesized by autotaxin (ATX) through its lysophospholipase D activity. Recent evidence suggests that the
ATX/LPA signaling axis plays a role in endometrial cancer. We carried out a prospective study involving two groups of
patients classifed in accordance to hysteroscopic-guided biopsy. Patients with histological diagnosis of endometrial cancer
were enrolled into group one, whereas control patients with pelvic organ prolapse were assigned group two. Both groups
underwent hysterectomy, with either open or laparoscopic surgery. After uterine extraction, a second endometrial biopsy
was performed to collect tissues. Real-Time PCR was performed to evaluate ATX gene expression in collected tissues. Sta-
tistical analysis including unpaired two-way or one-way Student’s t test and ANOVA was performed. We found ATX gene
expression signifcantly higher in neoplastic endometrium compared with normal tissue (P value = 0.0002). In particular,
the expression of ATX was signifcantly elevated in type I endometrial cancer (i.e., endometrioid histotype) compared to
type II, in premenopausal women and in patients afected either by obesity (BMI > 30) or diabetes. We propose ATX as a
novel potential biomarker particularly implicated in the pathobiology of type I endometrial cancer. Also, we propose ATX
as a useful theranostic target in endometrial cancer.
Keywords Autotaxin (ATX) · Endometrial cancer · Lysophosphatidic acid (LPA) · Biological marker · Obesity
Abbreviations
ATX Autotaxin
LPA Lysophosphatidic acid
RT Reverse transcription
PCR Polymerase chain reaction
BMI Body mass index
PTEN Phosphatase and tensin homolog
PIK3CA Phosphatidylinositol 3-kinase
KRAS Kirsten rat sarcoma virus
p53 Protein 53
HER-2/neu Human epidermal growth factor receptor 2/
proto-oncogene Neu
p16 Protein 16
PLD Phospholipase D
RNA Ribonucleic acid
DNA Deoxyribonucleic acid
GAPDH Glyceraldehyde 3-phosphate dehydrogenase
gene
SEM Standard error of the mean
SMB Somatomedin B-like
ENPP 2 Ectonucleotide pyrophosphatase/phosphodi-
esterase type 2
PLA2 Phospholipase A2
LPARs Lysophosphatidic acid receptors
* Antonio Mazzocca
antonio.mazzocca@uniba.it
1
Interdisciplinary Department of Medicine, University of Bari
School of Medicine, Piazza G. Cesare, 11, 70124 Bari, Italy
2
Interdisciplinary Department of Medicine, Gynaecology
and Obstetrics Clinic, University of Bari School of Medicine,
Piazza G. Cesare, 11, 70124 Bari, Italy
3
Department of Tissues and Organs Transplantation
and Cellular Therapies, D.E.O.T, School of Medicine,
University of Bari, Piazza G. Cesare, 11, 70124 Bari, Italy